[转帖]用系统生物学方法研究免疫响应

王不留行

用系统生物学方法研究免疫响应  

??系统生物学是利用由基因组学、蛋白组学和其他所有组学获得的数据来在一个比传统生物学更高的层次上分析活的生物体的一门学科，它被认为是解剖复杂系统的一个强大工具。但是此前，该方法在识别哺乳动物的基本机制方面并不是特别有效。免疫响应非常适合系统分析；小鼠模型也是非常成熟的模型，循环细胞也可以被纯化和培养。Gilchrist等人将系统生物学方法用于对由TLR4刺激的巨噬细胞进行动态模拟研究，并根据研究结果作出这样一个预测：转录因子ATF3在先天免疫响应中是一个负调控因子。所以，系统生物学工具很可能第一次揭示了免疫响应中一个新颖的调控机制和一个可能的药物作用新目标。




-=-=-=-=- 以下内容由 王不留行 在 2006年12月18日 10:17pm 时添加 -=-=-=-=-
系统生物学在免疫系统研究中的应用
信息来源：生物谷　更新时间：2004-7-21 3:20:00

   
Macrophages are found throughout the human body
Several decades of intensive study have revealed thousands of proteins that play important roles in the encounters between the immune system and pathogenic organisms. With the volumes of genomic information (both human and microbial) that are rapidly becoming available and the development of high-throughput analysis of mRNA and protein expression, protein modifications and protein-protein interactions, the field is at a turning point where major advances are likely to come from studies into how a multitude of proteins in many pathways interact with each other to coordinate our defense against infection.
The innate immune system also initiates local and sometimes systemic inflammatory responses that alert the body to the presence of potential threats and guides the development of subsequent adaptive immune responses that evolve in the weeks following infection. The inflammatory process is a double-edged sword; while on one hand inflammation is usually helpful and protective, it sometimes can become deregulated and result in tissue destruction and physiological changes that endanger the health of a person. Septic shock, a life-threatening systemic inflammatory response to bacterial infection, is a major problem in hospitals around the world, and inflammatory processes cause damage in a broad range of diseases including atherosclerosis, arthritis, and cancer.
Phagocytes such as macrophages, neutrophils, dendritic cells and monocytes are central effector cells of the innate immune system (see box). These cells constantly survey the body and recognize, internalize, kill and degrade foreign microbes. These cells also secrete inflammatory chemokines and cytokines and process antigens that train the adaptive immune response. The Aderem laboratory is focused on understanding the molecular and genetic factors that regulate these functions of phagocytes. How do macrophages detect microbes and identify infectious agents? A remarkable feature of the innate immune system is its capacity to recognize so many different types of microbes. Phagocytes use receptors belonging to several different genes families to bind microbes (see Figure 1 and Figure 2).These receptors permit the phagocyte to engulf and destroy the microbes. Some of the receptors are involved in the uptake/engulfment process, and others are involved in initiating the signals that announce to the immune system that microbes have been encountered.
How do immune cells internalize and kill microbes?
Phagocytosis is an ancient process by which phagocytes such as monocytes, macrophages, neutrophils and dendritic cells internalize large particles like bacteria or fungi and kill them. After recognition of a particle as foreign and potentially dangerous, signals are delivered into the phagocyte that cause reorganization of the actin cytoskeleton and recruitment and extrusion of membrane leading ultimately to complete enclosure of the particle within the phagocytes membranes. This newly formed compartment in the cell then matures into an acidic compartment where enzymes cause death and degradation of the potentially harmful organism. In addition to the central importance of phagocytosis to defense, internalization of dead cells and debris is also an important role of phagocytes in normal tissue maintenance and wound healing.




-=-=-=-=- 以下内容由 王不留行 在 2006年12月18日 10:19pm 时添加 -=-=-=-=-
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